Thromb Haemost 2020; 120(08): 1208-1216
DOI: 10.1055/s-0040-1713095
Stroke, Systemic or Venous Thromboembolism

Comparison of Effectiveness between Anticoagulation and Thrombolysis Therapy for Pulmonary Embolism in Patients Complicated with Shock: A Nationwide Population-Based Study

Jen-Kuang Lee*
1   Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
2   Department of Laboratory Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
3   Cardiovascular Center, National Taiwan University Hospital, Taipei, Taiwan
4   Telehealth Center, National Taiwan University Hospital, Taipei, Taiwan
,
Wen-Hsin Chen*
5   Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan
,
Yu-Sheng Lin
6   Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chaiyi, Taiwan
,
Chih-Hsiang Chang
7   Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
8   Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
,
Tien-Hsing Chen
5   Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan
6   Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chaiyi, Taiwan
9   Department of Medicine, Chang Gung University, Taoyuan, Taiwan
10   Biostatistical Consultation Center of Chang Gung Memorial Hospital, Keelung, Taiwan
› Author Affiliations
Funding This work was supported by grants from the Chang Gung Memorial Hospital, Taiwan (CGRPG2F0011, CLRPG2C0021, CLRPG2C0022, CLRPG2C0023, CLRPG2C0024, CLRPG2G0081, and CLRPG2G0082), the Ministry of Science and Technology of Taiwan (MOST 108–2221-E-002–163-), and National Taiwan University Hospital (107-EDN11, 108-N4406, 108EDN02, 109-O20, 109-S4579).

Abstract

Objective This study aimed to compare the efficacy of anticoagulation therapy and thrombolytic therapy for pulmonary embolism (PE) in patients complicated with shock.

Methods This retrospective cohort study used administrative data from Taiwan's National Health Insurance Research Database. Patients admitted due to PE who received inotropic support between January 1, 1997, and December 31, 2011, were included. To closely mimic a randomized experiment, anticoagulation and thrombolysis plus anticoagulation groups were subjected to propensity score matching (PSM) according to demographic characteristics, comorbidities, and inotropic agent dosage. The primary outcome was in-hospital mortality. The secondary outcome was 3-month mortality after discharge.

Results After PSM, a total of 820 patients, including 164 thrombolysis and 656 anticoagulation patients, were enrolled. The in-hospital mortality was 48.2% in the thrombolysis group and 52.4% in the anticoagulation group (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.59–1.18). Major bleeding occurred in 19 (11.6%) of the thrombolysis patients and 57 (8.7%) of the anticoagulation patients (OR 1.37, 95% CI, 0.79–2.38). The 90-day mortality rates in the thrombolysis and anticoagulation groups were 15.3% (13 patients) and 17.6% (55 patients), respectively; this difference was not significant (hazard ratio 0.88, 95% CI 0.48–1.61).

Conclusion In PE patients complicated with shock, anticoagulation therapy provides similar treatment efficacy to thrombolytic therapy in terms of in-hospital and 90-day mortality. The bleeding risk was also similar in the two treatment groups.

* Jen-Kuang Lee and Wen-Hsin Chen contributed equally to this study.


Supplementary Material



Publication History

Received: 23 March 2020

Accepted: 01 May 2020

Article published online:
17 July 2020

Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med 2011; 171 (09) 831-837
  • 2 Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353 (9162): 1386-1389
  • 3 Kucher N, Rossi E, De Rosa M, Goldhaber SZ. Massive pulmonary embolism. Circulation 2006; 113 (04) 577-582
  • 4 Hung CS, Lee JK, Yang CY. , et al. Measurement of visceral fat: should we include retroperitoneal fat?. PLoS One 2014; 9 (11) e112355
  • 5 Wu CK, Lee JK, Chiang FT. , et al. Plasma levels of tumor necrosis factor-α and interleukin-6 are associated with diastolic heart failure through downregulation of sarcoplasmic reticulum Ca2+ ATPase. Crit Care Med 2011; 39 (05) 984-992
  • 6 Konstantinides SV, Torbicki A, Agnelli G. , et al; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35 (43) 3033-3069
  • 7 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
  • 8 Meyer G, Vicaut E, Danays T. , et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014; 370 (15) 1402-1411
  • 9 Anderson HV, Willerson JT. Thrombolysis in acute myocardial infarction. N Engl J Med 1993; 329 (10) 703-709
  • 10 Hsing AW, Ioannidis JP. Nationwide population science: lessons from the Taiwan National Health Insurance Research Database. JAMA Intern Med 2015; 175 (09) 1527-1529
  • 11 National Health Insurance Administration MoH, Executive Yuan. National Health Insurance Annual Report; 2014
  • 12 Tsai T-C, Chen Y-C, Lo C-W. , et al. Incidence and renal survival of ESRD in the young Taiwanese population. Clin J Am Soc Nephrol 2014; 9 (02) 302-309
  • 13 Wang J-Y, Liu L-F. Health care utilization and medical costs for childhood asthma in Taiwan: using Taiwan National Health Insurance Research Database. Asia Pac Allergy 2012; 2 (03) 167-171
  • 14 Cheng SH, Chiang TL. The effect of universal health insurance on health care utilization in Taiwan. Results from a natural experiment. JAMA 1997; 278 (02) 89-93
  • 15 Cheng CL, Lee CH, Chen PS, Li YH, Lin SJ, Yang YH. Validation of acute myocardial infarction cases in the National Health Insurance Research Database in Taiwan. J Epidemiol 2014; 24 (06) 500-507
  • 16 Cheng CL, Chien HC, Lee CH, Lin SJ, Yang YH. Validity of in-hospital mortality data among patients with acute myocardial infarction or stroke in National Health Insurance Research Database in Taiwan. Int J Cardiol 2015; 201: 96-101
  • 17 Wu CK, Lin JW, Caffrey JL, Chang MH, Hwang JJ, Lin YS. Cystatin C and long-term mortality among subjects with normal creatinine-based estimated glomerular filtration rates: NHANES III (Third National Health and Nutrition Examination Survey). J Am Coll Cardiol 2010; 56 (23) 1930-1936
  • 18 Wu CK, Su MY, Lee JK. , et al. Galectin-3 level and the severity of cardiac diastolic dysfunction using cellular and animal models and clinical indices. Sci Rep 2015; 5: 17007
  • 19 Austin PC, Fine JP. Propensity-score matching with competing risks in survival analysis. Stat Med 2019; 38 (05) 751-777
  • 20 Jerjes-Sanchez C, Ramírez-Rivera A, Arriaga-Nava R. , et al; de Lourdes García M. Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial. J Thromb Thrombolysis 1995; 2 (03) 227-229
  • 21 Dotter CT, Seaman AJ, Rösch J, Porter JMJVS. Streptokinase and heparin in the treatment of pulmonary embolism: a randomized comparison. Vasc Surg 1979; 13 (01) 42-52
  • 22 Goldhaber SZ, Kessler CM, Heit J. , et al. Randomised controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. Lancet 1988; 2 (8606): 293-298
  • 23 Hao Q, Dong BR, Yue J, Wu T, Liu GJ. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev 2015; (09) CD004437
  • 24 Wu CY, Chen YJ, Ho HJ. , et al. Association between nucleoside analogues and risk of hepatitis B virus–related hepatocellular carcinoma recurrence following liver resection. JAMA 2012; 308 (18) 1906-1914
  • 25 Wu CK, Tsai HY, Su MM. , et al. Evolutional change in epicardial fat and its correlation with myocardial diffuse fibrosis in heart failure patients. J Clin Lipidol 2017; 11 (06) 1421-1431
  • 26 Marti C, John G, Konstantinides S. , et al. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J 2015; 36 (10) 605-614
  • 27 Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W. ; Management Strategies and Prognosis of Pulmonary Embolism-3 Trial Investigators. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002; 347 (15) 1143-1150
  • 28 Fasullo S, Scalzo S, Maringhini G. , et al. Six-month echocardiographic study in patients with submassive pulmonary embolism and right ventricle dysfunction: comparison of thrombolysis with heparin. Am J Med Sci 2011; 341 (01) 33-39
  • 29 Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet 2012; 379 (9828): 1835-1846
  • 30 Kuo WT, Gould MK, Louie JD, Rosenberg JK, Sze DY, Hofmann LV. Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern techniques. J Vasc Interv Radiol 2009; 20 (11) 1431-1440
  • 31 Kuo WT. Endovascular therapy for acute pulmonary embolism. J Vasc Interv Radiol 2012; 23 (02) 167-179
  • 32 Avgerinos ED, Chaer RA. Catheter-directed interventions for acute pulmonary embolism. J Vasc Surg 2015; 61 (02) 559-565
  • 33 Kucher N, Boekstegers P, Müller OJ. , et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014; 129 (04) 479-486
  • 34 Lip GY, Clementy N, Pericart L, Banerjee A, Fauchier L. Stroke and major bleeding risk in elderly patients aged ≥75 years with atrial fibrillation: the Loire Valley atrial fibrillation project. Stroke 2015; 46 (01) 143-150
  • 35 Voelkel N, Hubert ND, Backhaus R, Haberl RL, Hubert GJ. Thrombolysis in postoperative stroke. Stroke 2017; 48 (11) 3034-3039
  • 36 Chatterjee S, Chakraborty A, Weinberg I. , et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA 2014; 311 (23) 2414-2421
  • 37 Jiménez D, Aujesky D, Moores L. , et al; RIETE Investigators. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010; 170 (15) 1383-1389